1. Field of the Invention
The present invention relates generally to the field of targeted therapies. More particularly, it concerns compositions comprising fullerenes or nanotubes associated with antibodies or targeting peptides, and optionally further associated with therapeutic molecules.
2. Description of Related Art
In general, “targeted therapies” are therapeutic compositions and methods that involve the delivery of a drug to a particular diseased cell, tissue, organ, or organ system in a mammal, such as a human or a mammal providing esthetic, economic, or research benefits to humans. The benefits of a targeted therapy include the potential to use less of the drug and the minimizing of systemic side effects the drug may have on the mammal.
Antibodies, including monoclonal antibodies, and targeting peptides are known which engage in highly specific physical interactions with particular antigens.
Linking a therapeutic molecule directly to an antibody or targeting peptide has been attempted, but has encountered a number of difficulties. Frequently, the antibody or targeting peptide has multiple sites at which reaction with the therapeutic molecule can occur, and vice versa, and reaction at some of those sites can lead to changes in the drug's or the antibody or targeting peptide's structure and potentially impair its function. Also, if the therapeutic molecule's and the antibody or targeting peptide's active sites are free to move relative to each other (while remaining linked), the therapeutic molecule and the antibody or targeting peptide may interact physically or chemically (through favorable van der Waals interactions, hydrophobic interactions, hydrogen bonding, or ionic association, among others) and adopt conformations that change the structure and potentially impair the functions of the drug, the antibody or targeting peptide, or both.
Therefore, a need exists for improved compositions for use in targeted therapies.
Fullerenes, of which the best known example is C60, were first reported by Kroto et al., Nature (1985) 318:162. Since then, the ready derivatization of fullerenes has allowed a wide variety of derivatized fullerenes to be prepared and their properties explored.
Amphiphilic derivatized fullerenes have been reported by Hirsch et al., Angew. Chem. Int. Ed (2000) 39(10):1845-1848. The derivatized fullerenes of Hirsch comprised one dendrimeric group comprising 18 carboxylic acid moieties and five hydrophobic moieties each comprising a pair of lipophilic C12 hydrocarbon chains. Freeze-fracture electron micrography of aqueous solutions of the amphiphilic derivatized fullerenes revealed that the amphiphilic derivatized fullerenes formed bilayer vesicles (by which is meant, a vesicle defined by a membrane comprising an external layer of amphiphilic derivatized fullerene molecules substantially all oriented with their hydrophilic groups to the exterior of the vesicle, and an internal layer of amphiphilic derivatized fullerene molecules substantially all oriented with their hydrophilic groups to the interior of the vesicle, wherein the hydrophobic groups of the molecules of the external layer are in close proximity to the hydrophobic groups of the molecules of the internal layer) with diameters from about 100 nm to about 400 nm.
Carbon nanotubes and methods for their derivatization are known. Holzinger et al., Angew. Chem. Int. Ed. (2001) 40(21):4002-4005 report the cycloaddition of nitrenes, the addition of nucleophilic carbenes, and the addition of radicals, to the sidewalls of carbon nanotubes.